This invention relates to mass spectroscopy in general, and more particularly to an improved method and apparatus for carrying out ion cyclotron resonance spectroscopy.
High resolution mass spectrometry (MS) is used widely in chemistry for the elucidation of molecular structures and the study of numerous chemical and physical processes. A knowledge of an accurate mass measurement for an unknown molecule enables the chemist to reduce the number of possible structures to a short list. The resolution and mass-accuracy achievable with the most powerful of the commercial high resolution spectrometers does not yet eliminate entirely the need for interpretation of the spectrum and intuitive deduction by the chemist in arriving at a probable structure for a compound. Definitive structures for even moderately large molecules are rarely achieved and other forms of spectroscopy are usually needed to supplement the information obtained. The rate of advancement of the traditional scanning magnetic sector mass spectrometer has slowed due to technological limitations in magnet stability and the optical slits, and no dramatic improvements in resolution and mass-accuracy seem likely in the foreseeable future. Also, the recent improvements in chromatographic technology have surpassed the ability of the scanning magnetic sector instruments to obtain a spectrum in the time available (i.e. within the chromatographic peak width).
It has been recognized that ion cyclotron resonance (ICR) offers the greatest opportunity for major advances in the art of high resolution mass spectrometry. This is discussed by C. L. Wilkins and M. L. Gross in Analyl. Chem. 53, 1661-1668 (1981). For example, while the magnetic sector instrument achieves a resolution of ten thousand and a mass accuracy of 10 to 15 ppm in routine experiments ICR spectrometers commonly achieve a resolution exceeding one million and mass accuracies under 1 ppm. With this level of performance, completely unambiguous structure-determinations (excluding isomeric forms) should be possible for quite large molecules. In the ICR experiment, the ions are trapped by an applied electrostatic field and forced to undergo orbital (cyclotron and magnetron) motions at characteristic frequencies by the presence of a strong, uniform magnetic field.
The observable electrical signal arising from the motions of an ensemble of trapped ions of a single mass would be an exponentially-decaying sine wave (the rate of decay is determined by the frequency of collision between ionic and neutral molecules). For several different ionic masses, the ionic motions are reflected in a complex fluctuating signal made up of interferring sine waves of different frequencies and phases. This time-domain transient signal is often called an "interferogram" or simply a "transient." The individual frequency components of the interferogram are rendered observable by Fourier transformation, which is facilitated by digitizing the interferogram and storing its discrete binary representation in the memory of a digital computer where it can be processed numerically.
For a given mass observation range, the resolution and accuracy obtainable in the ICR experiment are limited by different factors, depending on the nature of the sample. In experiments with solid samples of low vapour pressure, the mass resolution is limited by the size of the digital memory available for storage of the interferogram, whereas, with chromatographic sources, the resolution is limited by the quality of the vacuum attainable in the mass analyzer. In either case, the accuracy of the measured masses is limited by the accuracy of the calibration function.
The two commerical ICR mass spectrometers available currently have several limitations. Routine use of gas and liquid chromatographic interfaces and a variety of modern ionization techniques are beyond the capability of the commercial ICR instruments. In these spectrometers, the ions are formed and mass-analyzed in the same region of physical space--inside a trapping cell 19 of about one cubic inch in volume. Mass-resolution in the ICR experiment increases with decreasing pressure and significant gains in performance are achieved only at working pressures of 10.sup.-8 torr or lower. The prior art instruments were designed with a fundamental limitation which renders them unsuitable for use with chromatographic-sample sources: it is impossible to inject a liquid or gaseous stream at near-atmospheric pressure into the ICR cell and maintain a satisfactory operating pressure for high resolution mass measurements. Consequently, applications of these instruments have so far been restricted in scope to solid-probe experiments.
In order to accomodate chromatographic sources, it is apparent that the ion source and detection regions must be spatially separated and differentially pumped to achieve the required ultra-high vacuum in the analyzer region. If satisfactory differential pumping can be achieved, the problem is reduced to one of transporting the ions to, and trapping them in, the ICR mass-analyzer cell.